Just because one is wealthy doesn’t mean they have the resources to cure a disease. All of the sufferers that have contributed data in this Forum not including the survey is more than any doctor or team could ever research in 50 years. If someone is going to find the cure or treatment it will be someone who wants it bad enough and who has the resources that is also sick with this rare disease.
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They aren’t saying that.
Below are direct quotes…
With all the limitations represented by the small cohort here considered for this emerging and rare syndrome, these results suggest that gut microbiota composition might represent a diagnostic marker and a possible target for a therapeutic strategy aimed to counteract the important symptomatology occurring in these patients.
On this basis, it is possible to hypothesize that gut microbiota changes observed in PFS patients may be ascribed to the alteration of steroid environment.
In addition, since as demonstrated in an experimental model of PFS, alteration of steroid environment also occurs in brain regions [28], the existence of a gut microbiota-brain axis [30,31,32] may also suggest a role by brain steroids. Finally, a possible contribution by intestinal steroid environment may be also hypothesized.
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I think its also good to be able to see the forest through the trees with some of this as far as possibilities.
While these initial studies or how they are looking at things might not seem that impressive atm, it could be a type of catalyst for things that may come down the line.
Example, I dont even need to see the study when it comes to seeing what could be possible, but ive probably looked at a few thousand. Id like to think of it as a type of machine learning that just keeps going, keeps peeling back the layers.
“A new study in mice led by UCLA biologists strongly suggests that serotonin and drugs that target serotonin, such as anti-depressants, can have a major effect on the gut’s microbiota”
I can give another example with Accutane, something I just read. It alters the skin microbiome.
They said the oil production comes back, the bacteria doesnt, its changed.
Maybe you could say the same thing with hormones as a growth or suppressor of certain microbes. They are saying that with ssri’s.
Maybe the hormones come back, the bacteria doesnt, or something else takes its place, just like with Accutane.
Microbial endocrinology: the interplay between the microbiota and the endocrine system
“only recently has a critical mechanism of bacterial interaction been revealed: modulation of hormonal secretion. From birth, bacterial colonization of the intestine has a role in the maturation of the immune system (Elahi et al. , [2013](javascript:;)) and the endocrine system (Clarke et al. , [2013](javascript:;)). Surprisingly, commensal bacteria can produce and secrete hormones. The crosstalk between microbes and hormones can affect host metabolism, immunity and behavior. This interplay is bidirectional, because the microbiota has shown to be both affected by and to affect host hormones,”
The microbiome as a target for endocrine disruptors: Novel chemicals may disrupt androgen and microbiome-mediated autoimmunity
novel synthetic and/or plant-derived chemicals may affect sex-biased autoimmune diseases through disruption of protective signaling networks between the microbiome and its host.
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Again, this is all I need to see right here to say “ok maybe.”
Neurological diseases very often lead to alterations of the intestinal microbiome. It is an indication of the disease. Obviously it is a consequence and not the cause. Melcangi obviously argues that this is a consequence. If he is one of the few doctors who understands something about the syndrome and if he claims that allopregnanolone will somehow help our condition the only thing I can do who lives in this condition is to trust him because the solution will not rain from heaven or other chosen minds. Obviously everyone can believe or not believe what he claims but I believe that a neuroendocrinologist rector of a university in Milan with multiple degrees and numerous researches on this condition by doing even invasive tests see examination on cerebrospinal fluid understands this condition more than anyone else. Because unlike others he has done studies … The others are perhaps doing them perhaps … Others say that a magic herb can heal … Unlike what is written above, he has made more publications and international collaborations. Obviously this is my humble thought which is just my humble opinion. Melcangi has studied the cerebrospinal fluid exams of the pudendal hormones and microbiome exams that have made tangible to verifiable … But this is always my thought I repeat … I give it a chance to melcangi … Being Italian having known having heard him speak I give my 500 euros to him with the hope that he promises to do what he thinks and hopes for. I repeat it is not a controversy with you indeed we are all in the same boat and this is just my personal opinion. A big hug to those who suffer like us.
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If only, just if only we could administer just one PFS sufferer SAGE-217 or another allopregnanolone analogue it could give us real insight into whether it helps or is a dead-end. That is an undertaking I would get behind.
The community is helplessly grappling for new avenues forward and options seem to be very limited. If there was a way to get this off the ground I would find a way to help out financially.
I hope I’m not violating any forum guidelines by making this post.
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We in the Italian community are raising funds for the study of melcangi. He claims that he will give us a hand and I want to believe it because hope is the only thing I have. I am 36 years old I had a beautiful youth I took off a drug and I fell into a mess.
I believe that even a cure for us is a great success … I know that I cannot go back to how I used to be but if there is only one single possibility of a cure I want to have hope. And the only one who can give it to me is Melcangi because he is one of the few perhaps the only one who does a real study and not based on the words of what happened. He has been studying for 15 years and maybe more … Sage 217 is a different thing is an analogue of allopregnonalone but it is not the same thing he said so too … He wants to test pure allopregnanolone on rats … Obviously he can’t do it about us … The studies involve a bureaucratic process no health ministry allows you to experiment with experimental drugs of a possible pathology not recognized on human beings. Because our difficulty is that PFS is not recognized by the scientific community and therefore the tests must be done on animals and rats are chosen for obvious reasons. Then the tests on rats give effect to the groups where the drug is tested. Maybe it is not the cure for all our problems maybe it is only partially but only by trying to do it you can say ok or not it goes if you stay still in 10 years we are always here if god wants to talk about tribulus rhodiola grass and others things that will never give a result to our conduct that can vary in intensity from subject to subject.
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@Preoccupato, I agree Melcangi attempted to do arguably more than anybody else to help understand PFS. My issue with Melcangi is I don’t believe the rats he uses have PFS.
Administering rats supraphysiologic doses of Finasteride does not give a rat PFS in the same way that probably close to 99% of human users of Finasteride do not suffer the symptoms of PFS.
My main concern is that Melcangi is not studying rats with PFS. Due to this I am very sceptical that his research will much utility to us - if anything it may actually lead us astray onto tangents.
What I’m looking for is an acknowledgement from Melcangi of the aetiology of PFS and how it is very distinct from an ordinary organism who has been administered Finasteride. So far it’s almost as though he is ignoring vital things in order to blindly proceed down his path. It’s like he has blinkers on in a sense. Once I have a satisfactory response and justification for any further research he is embarking upon I will be happy to contribute financially to the research effort.
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The only opportunity to experiment is the rat obviously cannot do on human beings and I shouldn’t repeat this, it seems obvious to me. If they test the covid vaccine where do they test it? First on animals and then on human beings. You will say but a rat and a rat a human and a human … I tell you and thank you it seems to me a disarming obviousness as a concept. He can reproduce the PFS on a rat … I don’t know … He tries and tries cmq to understand the similarities and the mechanisms so he moves and does something … doing something is better than doing nothing and waiting who knows thing from heaven. This is my point of view. He cannot experiment on humans … He can reproduce on several groups of rats a condition that can be identical, it can be slightly different or it can be totally different I am not a doctor and I don’t know this … The scientist is him and alone he can know and surely he knows more than me more than us in a general sense that we have neither the competence nor the knowledge because we don’t do either doctors or neuroendocrinologists or we have spent a whole life studying … even if we try to understand we do not have the means of knowledge that someone who has studied a life can have and this is an incontrovertible fact. We are not interested in our condition and if he shows a little interest in me it is obvious that a hope, even if moderate, lies in him. Then everyone is free to live life waiting for a possible solution in time as they want … doing something by trying something or helping or not helping someone who can or cannot solve the problem or partially try to do it with respect to the cosmic nothingness in which we are.
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Gosh yes that’s pretty painful. Was that your personal money or foundation money? Are the foundation funding Melcangi now even?
Obvious might be a strong word. Maybe we get farther if we dont assume too much in one direction.
Increasing clinical and preclinical evidence implicates the microbiome as a possible key susceptibility factor for neurological disorders , including Alzheimer’s disease , autism spectrum disorder, multiple sclerosis, Parkinson’s disease , and stroke.Nov 18, 2019
Changes to host microbiome composition coincide with neurologic changes affecting behavior, neurotransmitter levels, stress response, and gene expression in the brain [2,3,4,5]. These findings highlight a growing appreciation that gut bacteria may contribute to neuropsychiatric disorders, and potentially reveal attractive targets for translational studies in humans
Lets take it a step further, the microbiome as a possible key susceptibility factor for PFS. Maybe.
As far as SAGE, I have no desire for that coming from Accutane, it doesnt make sense to me. Thats just me though.
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Just critical thinking for a second (if you can call it that)…
Why do we need to know what the root cause is? And can you even find a “root cause”?. Isn’t the root cause taking an endocrine disruptor that has done end point damage (gut, brain, tissue…)? Searching for a root cause to me is like searching for an invisible man.
The gut is damaged, this we know.
The AR’s are deregulated
Neurosteroids are reduced
The prostate tissue may be messed up
Why can’t we focus on repairing the damage instead of looking for a root? What exactly are we looking for in this “root”? What are we expecting to find exactly? Say a gene is disregulated, or multiple genes are messed up. That could also represent a consequence of 5ari’s rather than this “root cause” that is causing the rest of the symptoms.
Maybe we can work on fixing the gut and then that will start a reverse feedback cycle an repair other things
Hope I’m making sense, I’m a philosopher, not a science guy…
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Of course the microbiome plays an important role in PFS/PSSD.
In a nature study this year scientists showed how the interplay of wrong genetics and l wrong gut bacteria decides over the course of neurogedenerative diseases such as ALS.
https://www.nature.com/articles/s41586-020-2288-7
Although I am tending rather to the position that the microbiome changes are consequences rather then causes, the opposite might be true and the microbiome rather than our genetics may predispose us to PFS/PSSD.
Anyways, this study delivered important insights into PFS. It is of sound reasoning that the microbiime changes that this study revealed contribute to further deterioration of the disease (butyrate is important for brain health and several strains are well-known for their association with depression).
It is also an important study to prove to the medic community that there are several pathological changes that cannot be ignored and cannot be explained by a nocebo effect.
Moreover the microbiome is a hot research topic. Therfore this study might draw international attention from the scientific community and may enable public research grants.
Yes, we have to look at the tissue specific androgen receptor expression, at the tissue-specific methylation of the AR-promotor, the aromatase complex and the SRD5a2. And there is no way around analysing post-mortem brain samples of PFS and PSSD patients.
But once again Melcangi delivered quickly and another result that helps with our understanding of this complex disease.
We have to admit no other researcher has done so much, so quickly and has revealed so many thinga as Melcangi. He has done more for our community than anyone else.
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I share Waytocure’s enthusiasm for Melcangi’s work.
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The choice is ours alone to live a life of waiting sitting and waiting for an unlikely solution that will rain from the sky … Maybe we will hypothetically find a drug for parkinson’s that has positive effects for our condition a little more as it has been discovered that finastris used for prostatic hypertrophy, it made hair grow … Or be involved in a research by the one who is currently the only person in the world who is doing studies and research to find at least a partial solution … I’ve already made my choice. If I have to die like this I want at least to die having actively tried to change my destiny instead of standing there waiting with his mouth open for a hypothetical solution that will come true by itself.
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Reparing the damage is like masking the symptoms.
You have erectionproblems? Take viagra.
You got gut problems? Eat healthy.
But as soon as you stop with either you go back to baseline set by the root cause, and that is why we need to find it and fix that.
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So what’s up next?
Melcangi’s work https://pubmed.ncbi.nlm.nih.gov/28408350/ showed that not only allopregnanolone is low, but also other hormones such as 17beta-estradiol = E2.
Some of you won’t care about E2, but recent studies show how important E2 is for male libido (the symptom that probably is least likely to ever have recovered in this forum!):
https://academic.oup.com/endo/article/161/10/bqaa137/5895007?searchresult=1
So how can this lowering of E2 in the CSF of PFS be explained? Surely not by methylation of SRD5a2… !?
Looking at the most frequent symptoms of PFS (including libido) it seems very likely that something is broken in the brain - and it must be something beyond 5-alpha-reductase - otherwise E2 would be elevated (!) - so how do we find out? What is next?
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A few thoughts here,
The Microbiome and Prostate Cancer Risk
There is now a host of evidence for a unique genitourinary (GU) microbiome.
Interestingly, the balance of inflammatory and anti-inflammatory bacterial lipopolysaccharides, production of bile salts, and metabolism of dietary fiber to short chain fatty acids all likely play important roles in creating systemic pro- or anti-carcinogenic states.
Sfanos et al. noted a unique microbial signature in patients undergoing oral androgen deprivation therapy (ADT)
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Good finding @guitarman01, it was even published in Nature. Here are the precise findings of Stefano et al.
" Differentially abundant species in the GI microbiota of men taking oral ATT
Since we observed significant differences in beta diversity by ADT status and type in PCoA, we next determined if particular species of GI microbiota were differentially abundant between medication categories. As shown in Table 2, several species of bacteria were differentially abundant in terms of the proportion of sequencing reads that matched the species/OTU obtained from the samples across different treatment categories. Notably, species, such as Akkermansia muciniphila , Ruminococcaceae spp., and Lachnospiraceae spp., were significantly more abundant in the fecal samples of men taking oral ATT. When analyzed at the bacterial family level, we again observed a significant greater abundance of sequencing reads assigned to the bacterial families Verrucomicrobiaceae (of which Akkermansia muciniphila is one of the few members), Lachnospiraceae , and others in the oral ATT group (Table [2]
(https://www.nature.com/articles/s41391-018-0061-x#Tab2)). There was also a significant decrease in the abundance of sequencing reads assigned to bacterial families such as Brevibacteriaceae , Erysipelotrichaceae , and Streptococcaceae in men receiving ADT versus no ADT and specifically in the oral ATT group versus men not undergoing ADT (Table 2)."
This is the original study of Stefanos et al. https://www.nature.com/articles/s41391-018-0061-x#Tab2
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Interestingly, while in androgen deprivation therapy Ruminococcaceae are enriched, Melcangi found the opposite, low Ruminococcaceae (maybe subspecies?!) in PFS.
That is something we should think about. How does that fit to the plasma steroid values Melcangi found in PFS? https://pubmed.ncbi.nlm.nih.gov/23890183/
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